Estimating the contribution of CD4 T cell subset proliferation and differentiation to HIV persistence

Daniel B. Reeves (), Charline Bacchus-Souffan, Mark Fitch, Mohamed Abdel-Mohsen, Rebecca Hoh, Haelee Ahn, Mars Stone, Frederick Hecht, Jeffrey Martin, Steven G. Deeks, Marc K. Hellerstein, Joseph M. McCune, Joshua T. Schiffer and Peter W. Hunt
Additional contact information
Daniel B. Reeves: Fred Hutchinson Cancer Center
Charline Bacchus-Souffan: Vir Biotechnology, Inc
Mark Fitch: University of California, University Avenue and Oxford St
Mohamed Abdel-Mohsen: The Wistar Institute
Rebecca Hoh: University of California
Haelee Ahn: University of California San Francisco
Mars Stone: Vitalant Research Institute
Frederick Hecht: University of California San Francisco
Jeffrey Martin: University of California San Francisco School of Medicine
Steven G. Deeks: University of California
Marc K. Hellerstein: University of California, University Avenue and Oxford St
Joseph M. McCune: Bill & Melinda Gates Foundation
Joshua T. Schiffer: Fred Hutchinson Cancer Center
Peter W. Hunt: University of California San Francisco

Nature Communications, 2023, vol. 14, issue 1, 1-13

Abstract: Abstract Persistence of HIV in people living with HIV (PWH) on suppressive antiretroviral therapy (ART) has been linked to physiological mechanisms of CD4+ T cells. Here, in the same 37 male PWH on ART we measure longitudinal kinetics of HIV DNA and cell turnover rates in five CD4 cell subsets: naïve (TN), stem-cell- (TSCM), central- (TCM), transitional- (TTM), and effector-memory (TEM). HIV decreases in TTM and TEM but not in less-differentiated subsets. Cell turnover is ~10 times faster than HIV clearance in memory subsets, implying that cellular proliferation consistently creates HIV DNA. The optimal mathematical model for these integrated data sets posits HIV DNA also passages between CD4 cell subsets via cellular differentiation. Estimates are heterogeneous, but in an average participant’s year ~10 (in TN and TSCM) and ~104 (in TCM, TTM, TEM) proviruses are generated by proliferation while ~103 proviruses passage via cell differentiation (per million CD4). In simulations, therapies blocking proliferation and/or enhancing differentiation could reduce HIV DNA by 1-2 logs over 3 years. In summary, HIV exploits cellular proliferation and differentiation to persist during ART but clears faster in more proliferative/differentiated CD4 cell subsets and the same physiological mechanisms sustaining HIV might be temporarily modified to reduce it.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-41521-1 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41521-1

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-41521-1

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().